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β-Casomorphins are a group of opioid peptides released during gastrointestinal digestion or food processing from the β-casein of milk protein. Consequently, milk can be divided into A1 and A2 “like” groups depending upon the presence or absence of proline or histidine at the 67th position of β-casein. A1 “like” milk is postulated to be a source of...
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... has 209 amino acids and there are at least 12 variants of this protein that differ at different amino acid positions. [14] As a result of a point mutation on exon VII of bovine β -casein gene on the sixth chromosome, a conversion from cytosine to adenine leads to replacement of proline (codon; CCT) by histidine (codon; CAT) at position 67. [15] The most common are A1 and A2 forms of β -casein based on the presence of amino acid histidine or proline respectively at position 67 of β -casein. A1 “like” milk involves β -casein with A1, B, C, F, and G alleles with the His 67 at residue 67 (-Tyr60-Pro61-Phe62-Pro63- Gly64-Pro65-Ile66-His67-) but variants at other positions of amino acids. A2 “like” milk (-Tyr60-Pro61-Phe62-Pro63-Gly64-Pro65-Ile66-Pro67-) has β -casein with A2, A3, D, H1, H2, and I alleles with a proline residue at 67 but variants at other positions of amino acids as shown in Fig. 1. [16,17] There are many DNA-based techniques, such as single stranded con- formational polymorphism (SSCP), [18] Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) [19] allele-specific PCR (AS-PCR), [17] real time PCR TaqMan, [20] and PCR-amplification created restriction site (PCR-ACRS) [21 − 23] to screen these alleles. Based on the A1 A2 hypothesis, milk can be classified into two types, i.e., A1 and A2 “like” depending on the presence of proline or histidine at the 67th position of the β -casein protein. It may seem surprising but this tiny difference in protein is postulated to produce a major effect in terms of BCM release. A1 “like” milk, i.e., milk containing β -casein variants that has histidine at the 67th position of the β -casein allows the cleavage at this position by different gastrointestinal enzymes to release BCM-7. A2 “like” has β -casein with a proline at this position and hinders the cleavage at this position and hence BCM-7 is not formed as shown in Fig. 2. BCM-7 was released after simulated gastrointestinal digestion (SGID) by pepsin, pancreatic elastase, and leucine amino peptidase. [24] Lotfi [25] produced BCMs from bovine β -casein by mild acid hydrolysis (pH 2.5, 37 ◦ C) with pepsin (1:100) and trypsin. De Noni [26] investigated the release of BCM-5 and BCM-7 during SGID of bovine β ...
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... One of the reasons for the downward trend was found to be the increasing popularity of plant-based dairy alternatives. Plant-based milks are white-coloured non-dairy beverages made from water-based extracts of plant materials ( health are equivocal, with some studies showing its benecial effect on mucus secretion, increased superoxide dismutase activity, etc (Trompette et al. 2003, Zoghbi et al. 2006, Yin, Miao, and Zhang 2010, ul Haq et al. 2014). In the current study, only about one-fth of the participants (n=231) knew about A1 and A2 milk, of which most people were unable to provide adequate details to make an informed decision about their consumption. ...
This study aims to understand the consumption patterns of milk and selected milk products in the Mumbai Metropolitan region. 1060 participants were interviewed about their milk consumption patterns including type of milk, frequency of consumption, amount consumed per day, attitudes towards milk products, and awareness and opinions regarding A1/A2 milk. 94.2% of participants were milk consumers, their average daily intake being 220±91ml. Only 5.8% of participants did not consume milk, primarily due to personal dislike. Among consumers, 57.3% consumed cow milk and 27.1% consumed buffalo milk. 88.7% of participants opined that milk is healthy. However, some consumers expressed concerns about milk adulteration. Of all, only 21.8% knew about A1/A2 milk but most could not provide details. These findings indicate an overall positive attitude of consumers towards milk and its continued inclusion in diets. Further studies and definitive steps are needed to resolve consumers' concerns about A1/A2 milk and milk adulteration.
... In addition to cheese-making properties effects, according to literature, β-CN A2, A3 and I are particularly interesting for human health, while variant A1 and B are supposed to be linked to undesired health effects. These negative variants are supposed to be widely diffused in Europe instead of β-CN A2 [2,18,33]. Indeed, literature data show that the European weighted mean value β-CN A2 allelic variant is 51.2 %, lower than America (70.6 %), Africa (61.0 %) and Asia (75.2 %), and very similar to Oceania (53.0 %) values (Table 6). Differently from what we expected, VRP, VNP and CAS breeds show higher value than the European one while HER breed show similar value. ...
Cow’s milk proteins are encoded by highly polymorphic genes characterized by several mutations which result in different allelic variants. Each allelic variant has different possible effects on cheese-making properties and on human health. β-casein A1-A3-I-B, k-casein B and β-lactoglobulin B are supposed to influence milk cheese-making properties by increasing cheese or milk yield, by varying chemical parameters, by having small casein micelle size, and by influencing rennet coagulation time (RCT) and curd-firming rate (CFR). In addition, β-casein A1-B are also considered to be a risk factor for different health diseases such as ischemic heart disease (IHD), type 1 diabetes (T1D), decreased glutathione (GSH) concentration, and milk intolerance. An LC-MS method was applied to profile, for the first time, the main milk proteins genetic variants from Aosta Valley autochtonous cattle breeds. Analyses performed on milk collected from bovines of three cattle breeds (Red Pied – VRP, Black Pied – VNP and Chestnut – CAS), either from IAR experimental farm or from herds of dairy-producers in Aosta Valley region, showed quite high frequencies of β-casein A2 and A3/I, and low frequencies of β-casein A1. Moreover, low frequencies of β-casein B in VRP breed and high frequencies of the same variant in CAS, and VNP breeds have been found. As far as k-casein is concerned allelic variant B is the most diffused in VRP while allelic variant A in VNP and CAS breeds. Finally, β-lactoglobulin most diffused allelic variant for all breeds is B. Results suggest that Aosta Valley milk has good cheese-making properties and good frequencies of β-casein A2 which may be related to beneficial effects on human health. In light of these results, it is important to develop breeding programs which take into consideration milk proteins polymorphisms to further increase the milk suitability for cheese-making process and to decrease the presence of β-casein A1 and B in drinking milk which can be a risk factor for human health.
Keywords: autochthonous cattle breed; genetic polymorphism; mass spectrometry; milk protein
... Однак, ймовірно внаслідок точкової мутації, 5000-10000 років тому у європейських стадах Bos taurus кодон САТ, що кодує гістин, утворився шляхом зміни нуклеотидної основи в кодоні ССТ, що кодує пролін, у 67-му положенні β-казеїну (Eigel et al., 1984;Elliott et al., 1988;Farrell et al., 2004). Так у європейських корів зʹявився один із варіантів β-казеїну -варіант А1 (Haq et al., 2014). ...
У статті описані результати дослідження гену бета-казеїну в популяціях сірої української породи корів, який асоціюється з молочною продуктивністю. Найбільш поширеними варіантами β-казеїну у молочних порід великої рогатої худоби є А1 та А2. Варіант CSN2А1 викликає серйозні відхилення в організмі людини, а саме: ряд патологічних порушень в роботі кишечника, ішемічну хворобу серця, діабет, аутизм у дітей. Аналіз наукових публікацій свідчить про те, що ген бета-казеїну (CSN2) не вивчений у аборигенних порід великої рогатої худоби України, які є носіями специфічних генних комплексів та більшості рідкісних алелей. Нами були проведені молекулярно-генетичні дослідження поліморфізму за локусом гену бета-казеїну в популяціях аборигенної сірої української породи з основних репродукторів даної породи в Україні. Геномну ДНК, виділену із цільної крові 173 тварин, ампліфікували з використанням праймерів, які створені на основі послідовностей гену CSN2 великої рогатої худоби. Ампліфікований фрагмент CSN2 довжиною 121 п.н. обробляли рестриктазою DdeI. В досліджених популяціях були виявлені всі три генотипи: гомозиготні CSN2А1А1, CSN2А2А2 та гетерозиготний CSN2А1А2. Аналіз результатів показав, що у корів ДП ДГ "Маркеєво" переважають носії гетерозиготного генотипу CSN2А1А2 (94,2%), генотип CSN2А2А2 відсутній. Результати генотипування ДП "Поливанівка" виявили, що 20% тварин є носіями генотипу CSN2А2А2, які дають А2 бета-казеїнове молоко. Переважав генотип CSN2А1А2, що визначався у 53% корів. Загалом, досліджена порода демонструє досить високий рівень "бажаного" алелю А2 – 0,468, при розчепленні якого не виробляється β-казоформін 7.
... β-casein (~30% of total casein) has 12 variants (A1, A2, A3, B, C, D, E, F, G, H1, H2, and I) that differ in their amino acid sequence. Most cattle breeds of European origin have a mix of these variants, while Guernsey and Jersey cows produce milk that has A2 as the major variant [1]. ...
... Среди генетических вариантов -казеина наиболее изучены А1 и А2 (46)(47)(48). Вариант А1 отличается от А2 лишь одной аминокислотой: в 67-й позиции замена цитозина на аденин привела к замещению пролина на гистидин (49)(50)(51). Выявление и количественный анализ -казеина А2 обязателен для молочных продуктов А2 (14,25,52). ...
... Среди генетических вариантов -казеина наиболее изучены А1 и А2 (46)(47)(48). Вариант А1 отличается от А2 лишь одной аминокислотой: в 67-й позиции замена цитозина на аденин привела к замещению пролина на гистидин (49)(50)(51). Выявление и количественный анализ -казеина А2 обязателен для молочных продуктов А2 (14,25,52). ...
... Вероятно, наряду с кишечной микробиотой формирование оси «кишечник -головной мозг» осуществляется и с помощью вышеописанных регуляторных пептидов, участвующих в нейрональной регуляции деятельности желудочнокишечного тракта [31,32]. Одной из разновидностей кисломолочных продуктов, содержащих казоморфины, являются детские йогурты, при закваске которых используются лактобактерии с определенными свойствами (наличие у микробов минимального количества фермента Х-пролилдиалипопептидилпептидазы, разрушающего казоморфины) [33,34]. ...
This review provides data on the use of yogurts in infants’ nutrition. The properties of these fermented milk products and associated urgent and delayed sanogenetic effects are described. The experience of yogurts (enriched with pre- and probiotics) implementation in the nutrition therapy of children who have undergone infectious diseases is shown. The yogurt usage for intestinal microbiota disorders correction in children with functional digestive disorders and chronic somatic pathology is discussed.
... Further research, involving human trials, must be carried out to decipher with confidence that the casein composition (A1/ A2) of milk is important for human health. In contrast, there are also some reports that suggested positive role of BCM7 like hypoglycemic effect, reduction in the oxidative stress and development of nephrophathy in diabetic rats, increased prolactin levels and gastrin expression, anticancer, opioid agonist, ACE inhibitory and immunomodulatory effects (Zong et al. 2007;Yin, Miao, and Zhang 2010;Zhang et al. 2012Zhang et al. , 2013Pepe et al. 2013;Ul Haq et al. 2014). Moreover, several antihypertensive peptides have been reported from casein protein and milk products, and the ACE-inhibitory activity of these peptides has been determined (Wu et al. 2013). ...
Bovine milk peptides are the protein fragments with diverse bioactive properties having antioxidant, anticarcinogenic, other therapeutic and nutraceutical potentials. These peptides are formed in milk by enzymatic hydrolysis, gastrointestinal digestion and fermentation processes. They have significant health impact with high potency and low toxicity making them a suitable natural alternative for preventing and managing diseases. Antibiotic resistance has increased the quest for better peptide candidates with antimicrobial effects. This article presents a comprehensive review on well documented antimicrobial, immunological, opioid, and anti-hypertensive activities of bovine milk peptides. It also covers the usage of computational biology tools and databases for prediction and analysis of the food-derived bioactive peptides. In silico analysis of amino acid sequences of Bos taurus milk proteins have been predicted to generate peptides with dipeptidyl peptidase IV inhibitory and ACE inhibitory properties, making them favorable candidates for developing blood sugar lowering drugs and anti-hypertensives. In addition to the prediction of new bioactive peptides, application of bioinformatics tools to predict novel functions of already known peptides is also discussed. Overall, this review focuses on the reported as well as predicted biologically active peptide of casein and whey proteins of bovine milk that can be utilized to develop therapeutic agents.
... Proteolytic cleavage of the A1 variant, with a histidine at position 67, leads to the release of a seven-amino acids peptide named -casomorphine 7 (BCM-7), with a strong opioid activity [4] . Regarding BCM-7 production, some casein variants ( "A1-like variants ", B, C, F and G) behave similarly to A1, while others ( "A2-like variants ", A3, D, E, H1, H2, I) behave like A2 [5] . Several studies reported a correlation between the presence of BCM-7 in milk or the "A1-milk " consumption and an increased risk for type 1 diabetes [6] , ischemic heart disease [7,8] , sudden infant death syndrome [9] , and increased gastrointestinal inflammation [10] . ...
A growing interest in the production and commercialization of A2 cow's milk has been observed in many countries in the last few years due to the beneficial properties for human health attributed to A2 β-casein variant. Methods of varying complexity and different equipment requirements have been proposed for the determination of the β-casein genotype of individual cows. We proposed herein a modification of a previously patented method based on an amplification-created restriction site PCR followed by restriction fragment length polymorphism analysis. This method allows to identify and differentiate A2-like from A1-like β-casein variants, after differential endonuclease cleavage flanking the nucleotide that determines the amino acid at position 67 of β-casein. The advantages of this method are that it:• enables to unequivocally score A2-like as well as A1-like β-casein variants,• can be performed at low cost in simply equipped molecular biology laboratories, and• can be scaled up to analyze hundreds of samples per day.For these reasons, and based on the results obtained from the analysis carried out in this work, it showed to be a reliable method for the screening of herds to selective breeding of homozygous cows and bulls for A2 or A2-like alleles.
... CSN2 A1/A2 allele is located on Chr.6, accession ID NC_037333.1 in assembly ARS-UCD1.3(GCF_002263795. 2) in which variation at region 6:85451298C>A (rs43703011) in exon 7 according to GenBank accession ID: M55158.1, transcript position 8101 with CDS c.245C>A , protein variant AAA30431.1 change the 67 th amino acid of β-casein polypeptide from proline (CCT, A2) to histidine (CAT, A1) [10]. ...
The cow is a very important mammal from the bovine family renowned for providing milk, meat and hide around the globe. β-casein is one of the principal proteins found in cows milk encoded by the CSN2 gene with 12-13 reported genetic variants present on Chr.6 in the cow genome. The current study investigated A1/A2 associated variant g.6:85451298C>A (rs43703011) in exon 7th according to the GenBank ID: M55158.1 position 8101C>A (c.245C>A), which is responsible to change the 67th amino acid of the β-casein polypeptide from proline (CCT, A2) to histidine (CAT, A1). The milk containing A2 protein variant is good while A1 milk has some negative effects on human health due to the production of β-casmomorphin-7. Genetic screening of the subject variant was conducted using ARMS-PCR on 48 native and exotic cows from Pakistan. Our initial results showed that 37.5% of the population is homozygous wild-type (C/C), 56.25% is heterozygous (C/A) and the remaining 6.25% is homozygous mutant-type (A/A). Additionally, the Chi-square association test was applied using the PLINK data analysis toolset which presented a significant p-value of 2.811×10-3 and OR of 3.8 with an alternative allele frequency of 0.2 and 0.5 in native and exotic populations respectively. Hence, there is significant variability in A1/A2 genotype which may be addressed by adopting selective breeding programs in Pakistan
